Hepatitis C Virus (HCV) infection is a major health problem accounting for significant morbidity and mortality. The importance of HCV infection lies in its propensity to cause insidious and progressive liver disease. An estimated 3.9 million of the citizens of this country are chronically infected by HCV. An incomplete understanding of the pathogenesis of HCV has limited the development of successful medical approaches to its treatment. Our laboratory has been focused on the characterization of the host immune response to HCV in patients with chronic HCV infection. This is based on the rationale that by understanding the host immune response, immune-based therapeutic interventions may be developed. Preliminary data suggest that HCV-specific cellular immune response play a direct role in disease pathogenesis and the control of viral spread, and may also participate in successful response to antiviral therapy. This proposal outlines an area of investigation that focuses on defining the role of the cellular immune system in the response to antiviral therapy. In addition, a new assay to define the antigenic region of HCV that is recognized by CD8+ cytotoxic T lymphocytes (CTL) will be developed. The long term goals of this proposal are: (1)To Determine the Functional Characteristics of the HCV-Specific CD4+ and CD8+ Response in Relation to Antiviral Therapy. (2)To Develop and Apply a Novel MHC Class I Peptide-Binding Assay To Predict CTL Epitopes In Patients With Chronic Hepatitis C. These studies will provide insight into basic immunologic principles associated with the host's immune response to this viral infection, as well as provide the basis for new interventional strategies.